Diltiazem and Penbutolol: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 9, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Diltiazem
Penbutolol
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
An increased risk of hypotension, bradycardia and slow AV conduction
Interaction Deep Dive
Concomitant use of dilTIAZem with beta-blockers may result in additive effects on cardiac conduction21. Concomitant use of dilTIAZem with beta blockers slows AV conduction and can increase the risk of bradycardia 1. DilTIAZem generally potentiates the pharmacologic effects of beta-adrenergic blocking agents, which may be useful in patients with normal heart function 3. However, hypotension, left ventricular failure, and AV conduction disturbances have been reported when dilTIAZem has been added to beta blocker therapy. This is more likely to occur in the elderly and in patients with left ventricular dysfunction, aortic stenosis, or those patients using large doses of either drug 4.
Why it happens (mechanism)
Additive cardiovascular effects, reduced metabolism of some beta blockers
Literature reports
6 reports — tap to read
a) DilTIAZem generally potentiates the pharmacologic effects of beta-adrenergic blocking agents, which may be useful in patients with normal heart function 3. However, hypotension, left ventricular failure, and AV conduction disturbances have been reported when dilTIAZem has been added to beta blocker therapy. This is more likely to occur in the elderly and in patients with left ventricular dysfunction, aortic stenosis, or those patients using large doses of either drug 4.
b) The hemodynamic tolerability and safety of high-dose intravenous dilTIAZem was evaluated in patients with coronary artery disease receiving long-term metoprolol treatment. DilTIAZem immediately decreased systemic vascular resistance, left ventricular systolic and mean aortic pressures (29%, 21% and 20%, respectively, at 5 minutes), and they remained significantly reduced at 30 minutes. There was little effect on heart rate or left ventricular contractility. PQ, QRS, and QTc intervals were not affected 5.
c) The effects of oral dilTIAZem and propranolol, alone and in combination with placebo were compared in 12 patients with stable-effort angina. No clinically significant depression of left ventricular function was found in this study. However, significant bradyarrhythmias and/or systemic hypotension were noted in five of 12 patients. Each case responded to a reduction in dosage of both dilTIAZem and propranolol. The authors concluded that "high-dose" dilTIAZem alone appears to be as effective as, or more effective, than moderate-dose propranolol or the combination of dilTIAZem and propranolol in improving exercise tolerance, myocardial ischemia, and left ventricular function in patients with stable-effort angina 6.
d) DilTIAZem (30 mg orally three times daily) increased the area under the concentration-time curve (AUC) of propranolol and metoprolol by 30% to 40% and also increased the elimination half-life of these drugs in 13 healthy volunteers 7. There was no effect on the plasma concentration of atenolol, a renally cleared beta blocking drug. dilTIAZem impaired the clearance of propranolol by inhibition of hepatic metabolism. Both d-propranolol and l-propranolol unbound clearance were decreased. In addition, propranolol significantly decreased the resting pulse rate after dilTIAZem pretreatment as compared to placebo. The pharmacokinetic interaction between these two drugs may also be related to this effect. Other hepatically metabolized beta blockers may be similarly affected 8.
e) In a randomized, double-blind, Latin-square, placebo-controlled design involving four separate treatments, eight healthy male Japanese volunteers received a single drop of timolol 0.5% or artificial tears in each eye with or without a single oral dose of niCARdipine 40 mg and with or without a single oral dose of dilTIAZem 60 mg. A single drop of timolol 0.5% reduced both heart rate and systolic blood pressure, showing evidence that ophthalmic timolol has systemic effects. Heart rate was increased after the administration of niCARdipine, and this effect was reduced by ophthalmic timolol following exercise. Concurrent administration of the timolol eyedrops and both calcium antagonists also reduced systolic blood pressure both at rest and during exercise 9.
f) Coadministration of dilTIAZem with propranolol in five normal volunteers resulted in increased propranolol levels in all subjects, and bioavailability of propranolol was increased approximately 50% 2.
Common questions
Can I take Diltiazem and Penbutolol together?
An increased risk of hypotension, bradycardia and slow AV conduction Always confirm with your pharmacist or prescriber before making any change.
How serious is the Diltiazem and Penbutolol interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Diltiazem or Penbutolol need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (9)
- Product Information: Lopressor(R) oral tablets, metoprolol tartrate oral tablets. Validus Pharmaceuticals LLC (per FDA), Parsippany, NJ, 2023. DailyMed
- Product Information: CARDIZEM(R) oral tablets, diltiazem hydrochloride oral tablets. Bausch Health US LLC (per FDA), Bridgewater, NJ, 2025. DailyMed
- Glasser SP, Friedman R, Talibi T, et al: Safety and compatibility of betaxolol hydrochloride combined with diltiazem or nifedipine therapy in stable angina pectoris. Am J Cardiol 1994; 73:213-218. PubMed
- Sagie A, Strasberg B, Kusnieck J, et al: Symptomatic bradycardia induced by the combination of oral diltiazem and beta blockers. Clin Cardiol 1991; 14:314-316. DOI
- Wiesfeld AC, Remme WJ, Look MP, et al: Acute hemodynamic and electrophysiologic effects and safety of high-dose intravenous diltiazem in patients receiving metoprolol. Am J Cardiol 1992; 70:997-1003. PubMed
- Hung J, Hackett PL, Gordon SPF, et al: Pharmacokinetics of diltiazem in patients with unstable angina pectoris. Clin Pharmacol Ther 1988; 43:466-470. DOI
- Tateishi T, Nakashima H, Shitou T, et al: Effect of diltiazem on the pharmacokinetics of propranolol, metoprolol and atenolol. Eur J Clin Pharmacol 1989; 36:67-70. PubMed
- Hunt BA, Bottorff MB, Herring VL, et al: Effects of calcium channel blockers on the pharmacokinetics of propranolol stereoisomers. Clin Pharmacol Ther 1990; 47:584-591. DOI
- Yatsuka YI, Tsutsumi K, & Kotegawa T: Interaction between timolol eyedrops and oral nicardipine or oral diltiazem in healthy Japanese subjects. Eur J Clin Pharmacol 1998; 54:149-154. PubMed
Keep reading about Diltiazem
Keep reading about Penbutolol
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